Infection with antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a dangerous and costly complication of broad-spectrum antibiotic therapy1, 2. How antibiotic-mediated elimination of commensal bacteria promotes infection by antibiotic-resistant bacteria is a fertile area for speculation with few defined mechanisms. Here we demonstrate that antibiotic treatment of mice notably downregulates intestinal expression of RegIIIgamma (also known as Reg3g), a secreted C-type lectin that kills Gram-positive bacteria, including VRE. Downregulation of RegIIIgamma markedly decreases in vivo killing of VRE in the intestine of antibiotic-treated mice. Stimulation of intestinal Toll-like receptor 4 by oral administration of lipopolysaccharide re-induces RegIIIgamma, thereby boosting innate immune resistance of antibiotic-treated mice against VRE. Compromised mucosal innate immune defence, as induced by broad-spectrum antibiotic therapy, can be corrected by selectively stimulating mucosal epithelial Toll-like receptors, providing a potential therapeutic approach to reduce colonization and infection by antibiotic-resistant microbes.

absolute risk reduction of 31,5% in antibiotic exposure; one in every four patients who were admitted to the hospital due to an AECOPD, one course of antibiotic therapy can be prevented (NNTT 3.2)

Industrial penicillin production with the filamentous fungus Penicillium chrysogenum is based on an unprecedented effort in microbial strain improvement. To gain more insight into penicillin synthesis, we sequenced the 32.19 Mb genome of P. chrysogenum Wisconsin54-1255 and identified numerous genes responsible for key steps in penicillin production. DNA microarrays were used to compare the transcriptomes of the sequenced strain and a penicillinG high-producing strain, grown in the presence and absence of the side-chain precursor phenylacetic acid. Transcription of genes involved in biosynthesis of valine, cysteine and alpha-aminoadipic acid—precursors for penicillin biosynthesis—as well as of genes encoding microbody proteins, was increased in the high-producing strain. Some gene products were shown to be directly controlling beta-lactam output. Many key cellular transport processes involving penicillins and intermediates remain to be characterized at the molecular level. Genes predicted to encode transporters were strongly overrepresented among the genes transcriptionally upregulated under conditions that stimulate penicillinG production, illustrating potential for future genomics-driven metabolic engineering.

Dutch researchers have decoded the DNA sequence of the fungus which produces penicillin. It is hoped that uncovering the genome of Penicillium chrysogenum will boost the development of new antibiotics to overcome problems of resistance. The findings come just in time for the 80th anniversary of the discovery of penicillin by Sir Alexander Fleming.

In microorganisms, menaquinone is an obligatory component of the electron-transfer pathway. It is derived from chorismate by seven enzymes in Escherichia coli. However, a bioinformatic analysis of whole genome sequences has suggested that some microorganisms, including pathogenic species such as Helicobacter pylori and Campylobacter jejuni, do not have orthologs of the men genes, even though they synthesize menaquinone. We deduced the outline of this alternative pathway in a nonpathogenic strain of Streptomyces by bioinformatic screening, gene knockouts, shotgun cloning with isolated mutants, and in vitro studies with recombinant enzymes. As humans and commensal intestinal bacteria, including lactobacilli, lack this pathway, it represents an attractive target for the development of chemotherapeutics.

FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian β-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi-drug–resistant Staphylococcus aureus. The putative inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti-staphylococcal therapy.

The need for new antibiotics is undisputed (1). Recent studies estimate that more people die from the methicillin-resistant Staphylococcus aureus (MRSA) bacterium than from HIV in the United States (2), and the Centers for Disease Control and Prevention estimates that more than 90,000 people die from hospital-acquired bacterial infections in the United States each year. Numerous reports have illustrated the "perfect storm" of rising bacterial resistance to antibiotics and an industry pipeline ill-equipped to address the need for new antibacterial drugs (3, 4) (see the figure). Consequently, the reports by Haydon et al. on page 1673 in this issue (5) and by Rasko et al. (6) are important because they validate and illustrate the therapeutic potential of two new antibacterial drug targets. In addition, the paper by Hiratsuka et al. on page 1670 in this issue (7) identifies a biosynthetic pathway that may provide new antibacterial strategies for certain species of bacteria.

Giving women antibiotics to delay premature labour may increase the risk of developmental problems for the baby, a study suggests. The study by the University of Leicester, published in The Lancet, assessed seven-year-olds whose mothers had been involved in a clinical trial at the time of their birth. The children of those given an antibiotic were much more likely to have cerebral palsy. The Health Department has written to doctors asking them to discontinue the practice, which is not routine. Experts say that the more common use of antibiotics for pregnant women who show signs of an infection when their waters break early can be lifesaving, and should be continued. Many new mothers get too little postnatal support, a poll of 6,000 mothers by Netmums.com found. Six out of ten felt they had not seen their health visitor enough during the first year of their child’s life.

A warning about the indiscriminate prescribing of antibiotics to pregnant women to delay premature labour was issued to all doctors yesterday after research unexpectedly revealed that the practice may cause long-term harm to their babies. The Government's chief medical officer, Sir Liam Donaldson, wrote to GPs, obstetricians and other medical staff following publication of the first study of the subject. The findings show an increased risk of cerebral palsy in the children of one group of women. There was also a small increase in problems such as poor eyesight or hearing. The results add to the growing evidence that what happens in the womb has a huge impact on the baby not only at birth but for decades beyond.